Thyroid hormones

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• Thyroid hormones
• and
• antithyroid drugs

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• normal amount of thyroid hormones are essential
  for normal growth and development by maintaining
  the level of energy metabolism in the tissue.
• Either too little or too much thyroid hormones
  will bring disorders to the body.

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Part 1 Thyroid hormones

• Two major thyroid hormones are
• triiodothyronine(T3, the most active form)
• thyroxin(T4)
• The characteristic of their chemical structure is
  that they all contain iodine as an essential part
  of the molecule.

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Structure
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• inadequate secretion of thyroid hormone
  (hypothyroidism) can bring many disorders to the
  body (eg. bradycardia, poor resistance to cold,
  both mental and physical slowing.)

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• Synthesis, storage and release of thyroid
  hormones

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Synthesis

• Iodine is the raw material of the thyroid
  biosynthesis. Once taken up by the thyroid gland,
  iodine undergoes a series of enzymatic reactions
  before it converts into active thyroid hormones.

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Synthesis four steps

• 1. iodine trapping uptake of iodine by the
  thyroid gland
• 2. oxidation of iodine (to its active form)
• thyroid peroxidase (key enzyme of the
  synthesis)
• 3. iodide organification the iodination of
  tyrosyl groups of thyroglobulin
• productions MIT and DIT
• 4. formation of T4 and T3 from MIT and DIT
• thyroid peroxidase

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storage

• store in the colloid droplets of thyroglobulin

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release

• The hormones are released by proteolysis of
  thyroglobulin .
• Enzyme thyroglobulin hydrolase
• The ratio of T4 to T3 within thyroglobulin is
  about 51

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Differences between T3 and T4

• the effect of T3 is much faster, stronger and
  shorter than that of T4.

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conversion

• T4 can converse to T3 through deniodonite in
  peripheral tissues as well as in the thyroid.
• (catalyzed by deiodinase)

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Regulation
TRH
Hypothalamus
pituitary
TSH
T3,T4
thyroid
Controled by HPT(hypothalamic-pituitary-thyroid)
axis
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Regulation
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TRH (thyrotropin releasing hormone) TSH
(thyroid stimulating hormone or thyrotropin)
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Pharmacokinetics
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Pharmacological actions

• Effects on growth and development
• Calorigenic effects
• Hypersensitivity to catecholamine

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Pharmacological actions

• 1.Effects on growth and development
• responsible for normal growth and maturation
  of human being , especially for nervous and
  skeletal tissues.
• so the absence of thyroid hormones before
  birth leads to both mental and physical
  retardation(cretinism)

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Pharmacological actions

• 2.Calorigenic effects
• T3 /T4 can increase oxygen consumption, promote
  metabolism and BMR(basal metabolic rate)
  ,?utility.
• So hyperthyroidism will result in excess heat
  production and body wasting.

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Pharmacological actions

• 3. hypersensitivity to catecholamine
• Cardiovascular effects
• Tachycardia, hypertension
• nervous Effects anxiety, nervous.

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mechanism

• TR
• CBP
• NUCLEAR R

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Clinical uses

• the major indications for the therapeutic use of
  thyroid hormones are for hormone replacement
  therapy in patients with hypothyroidism .

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Clinical uses

• 1.Cretinism congenital hypothyroidism
• often happens in newborn babies, mainly caused by
  iodine deficiency before birth .
• Success in the treatment of cretinism depends on
  the age at which therapy is started.
• The earlier, the better.

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Cretinism

• Symptoms
• 1.Physical slow
• dwarf, with short extremities ,
• 2.mentally retarded inactive, uncomplaining and
  listless.
• incidence about 1 per 400 births
• Prevention and therapy
• Prevention Iodine replacement is the best method
  prior to pregnancy.
• Therapy thyroid hormones replacement(T4 is more
  often used than T3)

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Clinical uses

• 2.Myxedema adult hypothyroidism
• Happens after individual development
• Slow in mentality
• With special edema
• Mortality 60

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Clinical uses

• 3.Simple goiter
• A kind of prevalent disease caused by
  insufficient dietary iodine
• TSH can promote hyperplasy and hypertrophy of
  thyroid gland.
• 4. Differential diagnosis of simple goiter and
  hyperthyroidism

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Simple goiter
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adverse reactions

• hyperthyroidism

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• Part 2
• Antithyroid drugs

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Graves syndrome
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Treatment of hyperthyroidism

• The goal of therapy is to decrease the additional
  hormone and attend to normal levels.
• Can be accomplished by
• removing part of the gland
• Inhibiting synthesis
• Blocking releasing

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four categories of anti-thyroid drugs

• ? Thioureas (???)
• interfere directly with the synthesis of
  thyroid hormones
• ? High concentrations of iodine
• decrease the release of thyroid hormones
• ? Radioactive iodine
• damage the gland with ionizing radiation
• ? ß- receptor antagonists
• control the manifestations

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? Thioureas(???)

• Thiouracils
• methythiouracil , propylthiouracil
• Imidazoles
• methimazole , carbimazole.

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? Thioureas

• Pharmacological action
• Decrease the level of thyroid hormones
• Mechanism
• 1.inhibit the thyroid peroxidase
• (key enzyme of synthesis)
• interfere the oxidation of iodine and the
  coupling of MIT and DIT to form T3/T4

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• 2. inhibit conversion from T4 to T3
• 3.immunosupressive effect TSI

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• Pharmacokinetics
• Absorption
• Distribution
• Excretion
• Pass through placenta, milk

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Therapeutic uses

• 1.As definitive treatment to control
  hyperthyroidism
• 2.Preoperative preparations for subtotal
  thyroidectomy to control the disorder in
  preparation for surgical treatment.
• (thioureas plus large dose of iodine)
• 3. Thyroid crisis Propylthiouracil is the first
  choice.

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Adverse reactions

• 1.allergic response
• 2.GI reaction
• 3.granulocytopenia (0.3-0.6)
• 4.Longterm use
• goiter and hypothyroidism

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Drug interactions

• ?
• Li,sulfasulfonamide,PAS,paraminan(?????),phe
  nylbutazone,barbital,phentolamine,sulfonyl
  urea,vitB12
• ?
• iodine

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? Iodine and iodide

• Oldest agent
• have completely different effects due to
  different doses

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Pharmacological effects

• in small dose
• ? synthesis of thyroid hormones
• in large dose antithyroid
• 1) ?the release of thyroid hormones into the
  circulation strong
• Mechanism Inhibit thyroglobulin hydrolase
• 2)?synthesis of thyroid hormones weak
• Mechanism Inhibit thyroid peroxidase

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Therapeutic uses

• 1.Simple goiter in small dose
• 2.In preparation for thyroidectomy
• used after the hyperthyroidism has been
  controlled by thioureas, given for 7 to 10 days
  immediately preceding the operation. (The changes
  after a fairly long term of administration
  include the vascularity of the thyroid gland is
  reduced, the gland becomes much firmer and
  smaller.)
• 3.Thryotoxic crisis

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Adverse reactions

• 1. Chronic iodism
• 2.Acute allergic action
• angioneurotic edema and larynx edema
• 3. Thyroid dysfunction

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? Radioactive iodine

• 131I most often used isotope of iodine
• ? rays(1)
• ß particles(99) destructive

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Effects on the thyroid gland

• 131I is rapidly and efficiently
  trapped by the thyroid gland and slowly
  emitsßparticles and ?rays.
• The destructive ßparticles can
  destroy the thyroid cells with little damage to
  surrounding tissues (the penetration range is
  only 0.4-2.0mm).
• The?rays can pass through the tissue
  and be quantified by external detection

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Clinical uses

• 1.hyperthyroidism administrated orally and
  the effective dose differs for individual
  patients.
• 2.diagnosis of thyroid functions

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• Adverse reactions
• hypothyroidism
• contraindications
• pregnancy and milk mothers

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IV ß-adrenergic receptor antagonists

• ------ adjuvant therapy
• many of the symptoms of hyperthyroidism are
  associated with sympathetic stimulation, so ß-R
  blockers are effective in antagonizing the
  catecholaminegic symptoms such as tachycardia,
  palpitations ,anxiety and tension.

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• Action
• (1)block ?1-R of heart
• (2)block ?-R of CNS
• (3) block ?-R of presynaptic membrane of
  peripheral nerve.
• (4) Inhibit T4 converted into T3

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• Uses
• 1.Control the symptoms of
• hyperthyroidism before
• confirmed diagnosis
• 2.Thyroid crisis
• 3.Preoperation of hyperthyroidism
• 4.Hyperthyroidism

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• Section 3
• TSH and TRH

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Thank you!